The long-term goal of this project is to develop an anti-cancer drug, based on the prototype compound suramin that would allow widespread use in humans with a variety of cancer types. Clinical studies with suramin in hormone refractory prostate cancer have shown significant response rates through Phase II studies. However, severe toxicities have been observed that are treatment limiting and the narrow window between active and toxic drug levels precludes suramin use in some cancers or in combination with other anti-cancer agents. We plan to overcome these problems with suramin by identifying derivatives that maintain the anti- cancer activity but have reduced toxicity. Preliminary studies have identified a set of five compounds that have increased potency in growth factor inhibition and prostate tumor cell growth. These compounds will be assessed for tumor growth inhibition in vivo with human tumor cell xenografts in mice. In addition, a preliminary assessment of toxicity will be determined in order to evaluate the therapeutic index. Successful completion of this project may lead directly to a new clinical candidate for treatment of prostate and other solid tumors. PROPOSED COMMERCIAL APPLICATION: The work may lead to an improved treatment for hormone refractory prostate cancer. This would potentially also provide a new treatment for other cancers currently without any effective therapy.